Physicians rely on personal examination and clinical laboratory results to determine the presence and concentration of biological analytes in critical care patients. Clinical laboratories offer a wide range of automated systems for high-volume testing and analytical support in a well controlled, high quality environment. However, clinical laboratories can not provide the immediate results needed to properly treat trauma and multi organ dysfunction/failure patients.
To meet the clinical need for immediate test results, several technologies are emerging for testing using reliable, automated analyzers at the patient's bedside including electrochemical biosensors, optical fluorescence sensors, paramagnetic particles for coagulation test systems, and micromachined devices for both chemical and immunochemical testing. These technologies have allowed multi-analyte chemistry panels to be performed rapidly and have addressed previous obstacles such as calibration of test devices.
These tests can be classified as: 1) in vitro, which is performed at the bedside; 2) ex vivo or para vivo, which is performed at wrist-side; and 3) in vivo, which is performed inside the patient. Such tests offer indirect cost efficiencies and savings such as reduced labor costs, decreased blood identification and transport errors, and reduced patient complications.
In vitro or bedside devices are used typically in several departments of the hospital including intensive care units; operating rooms; emergency departments (ER); interventional departments; general patient care departments; and outpatient surgery and ambulatory care units. In vitro diagnostic tests offer a wide range of diagnostic tests, similar to the clinical laboratory. In vitro diagnostic test systems typically are not connected on-line to the patient and require an operator for blood sampling.
Key categories of diagnostic test in the diagnostic market include arterial blood gases, blood chemistries, blood glucose, coagulation, drugs-of-abuse testing, hemoglobin hematocrit, infectious diseases, and therapeutic drug monitoring. Other categories include cancer markers, cardiac markers, cholesterol detection, immunodiagnostics, infectious disease detection, lactate, and thrombolytic monitoring.
Ex vivo diagnostics use external sensors for on-line real-time testing with little to no blood loss. Typically, sampled blood flows through a closed system to minimize blood contact. Ex vivo system minimize problems associated with in vivo sensors, including clotting, inaccuracy, calibration drift, and an inability to recalibrate once in the patient. U.S. Pat. No. 5,505,828 discloses an exemplary ex vivo system.
In vivo diagnostics offer considerable potential in the treatment of most critical and unstable patients. Although many companies are developing in vivo sensors, technical hurdles have thus fair kept in vivo sensors from common commercial use.
Ex vivo and in vivo diagnostics, since they are on-line systems, can reduce quality control and information integration errors that occur with clinical or in vitro tests. Quality control errors are commonly due to operator errors, not instrument errors or device failures. Exemplary errors include inappropriate specimen volume, inaccurate calibration, use of deteriorated test strips, inadequate validation, insufficient instrument maintenance, bad timing of the test procedure, and use of the wrong materials. Clinical information system integration allows test data collected at the bedside to be put directly into the patient record. This improves the efficiency of the patient management process, allowing the integration of the laboratory's information system and clinical information systems, providing a “seamless” flow of all types of patient information.
Lactate is the byproduct of carbohydrate metabolism and product of glycolysis (pyruvate) is converted into lactate under an aerobic condition i.e. deficiency of oxygen in cells. Lactate estimations are therefore important in respiratory disorder, heart ailment, labor diseases etc. The normal concentration of lactate in human blood is in the range of 1.2 to 2.7 mM.
Procedure for lactate determination for example, has employed a variety of chemical and physical technique. Traditional assay involves chemical treatment of lactate in human blood and thereby converting it into colour products which can be measured spectrophotometrically, the methods consists in reacting the blood under test with enzyme namely lactate dehydrogenise (LDH). In such process absorbance at 340 nm is measured due to the NADH formation, it becomes a measurement of lactate originally present in blood.
U.S. Pat. No. 6,117,290 discloses an on-line lactate sensor arrangement. The sensor arrangement includes a lactate sensor, a catheter for withdrawing a test sample, and a first fluid flow line provided fluid communication between the lactate sensor and the catheter. The sensor arrangement also includes a source of sensor calibration and anticoagulant solution, and second fluid flow line providing fluid communication between the source of sensor calibration and anticoagulant solution and the lactate sensor.
In practice there are some difficulties in adopting such a detection procedure for use with blood sample. The disadvantage of such methods, include, lack of specificity, difficulty of standardization, requirement of large amount of blood and use of unstable and corrosive regents. Such methods also involve optical detection and are therefore expensive and time consuming. Additionally, the samples must be prepared. Another disadvantage is that the measurement of lactate level by prior art methods need to be done in laboratory by qualified personnel.
Asha Chaubey et al disclose in Electrochimica Acta Vol 46, 723-729 (2000) the immobilization of lactate dehydrogenase on electrochemically prepared polypyrrole polyvinyl sulphonate composite films. The response time reported is about 40 seconds and a shelf life of about 2 weeks under refrigerated conditions. In another disclosure (Asha Chaubey et al, Analyticla Chimica Acta Vol 49, 98-103, 2000), the immobilization of lactate dehydrogenase on conducting polyaniline films is disclosed. The linearity of response is shown from 0.1 mM to 1 mM lactate concentration with a shelf life of about 3 weeks under refrigerated conditions. It is preferable to obtain sensors with longer shelf life and shorter response time.
Accordingly, it is important to provide a lactate biosensing strip that can overcome the disadvantages of the prior art without losing out on efficiency and accuracy of measurement.